Nanobodies to Study G Protein-Coupled Receptor Structure and Function.

TitleNanobodies to Study G Protein-Coupled Receptor Structure and Function.
Publication TypeJournal Article
Year of Publication2017
AuthorsManglik, A., B. K. Kobilka, and J. Steyaert
JournalAnnu Rev Pharmacol Toxicol
Volume57
Pagination19-37
Date Published2017 01 06
ISSN1545-4304
KeywordsAnimals, Dose-Response Relationship, Drug, Humans, Isoproterenol, Ligands, Protein Binding, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, G-Protein-Coupled, Single-Domain Antibodies
Abstract

Ligand-induced activation of G protein-coupled receptors (GPCRs) is a key mechanism permitting communication between cells and organs. Enormous progress has recently elucidated the structural and dynamic features of GPCR transmembrane signaling. Nanobodies, the recombinant antigen-binding fragments of camelid heavy-chain-only antibodies, have emerged as important research tools to lock GPCRs in particular conformational states. Active-state stabilizing nanobodies have elucidated several agonist-bound structures of hormone-activated GPCRs and have provided insight into the dynamic character of receptors. Nanobodies have also been used to stabilize transient GPCR transmembrane signaling complexes, yielding the first structural insights into GPCR signal transduction across the cellular membrane. Beyond their in vitro uses, nanobodies have served as conformational biosensors in living systems and have provided novel ways to modulate GPCR function. Here, we highlight several examples of how nanobodies have enabled the study of GPCR function and give insights into potential future uses of these important tools.

DOI10.1146/annurev-pharmtox-010716-104710
Alternate JournalAnnu. Rev. Pharmacol. Toxicol.
PubMed ID27959623
PubMed Central IDPMC5500200
Grant ListR01 GM083118 / GM / NIGMS NIH HHS / United States
R01 NS028471 / NS / NINDS NIH HHS / United States
T32 GM008294 / GM / NIGMS NIH HHS / United States
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